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Which subchondral bone measure is the best predictor of cartilage damage?
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Abstracts / Bone 44 (2009) S142–S161
performance liquid chromatography. Non-parametric tests were used (Spearman coefficient correlation r′). Linear crack density (#/mm2) and diffuse damage area density (%) increased with age (r′ = 0.36, p = 0.01, r′ = 0.32, p = 0.022, respectively), as did the PYD/DPD ratio (r′ = 0.31, p = 0.028). Elastic modulus and ultimate strength decreased with age (r′ = − 0.36, p = 0.01, r′ = − 0.39, p = 0.01, respectively), whereas post-yield strain was unchanged. BV/TV was strongly correlated with elastic modulus (r′ = 0.66, p < 0.001) and ultimate strength (r′ = 0.74, p < 0.001). The elastic modulus was weakly correlated to mean crack length (r′ = 0.30, p = 0.036), but otherwise not associated with pre-existing microdamage. Collagen cross-link concentrations were not associated with mechanical properties. PYD concentration was positively correlated to linear microcrack density (r′ = 0.33, p = 0.017) and to total microcrack density (r′ = 0.36, p = 0.008), whereas PYD and DPD were negatively correlated to mean microcrack length (r′ = − 0.30, p = 0.029 and r′ = − 0.28, p = 0.046, respectively). PEN concentration was not associated with microdamage. In summary, this study of trabecular bone from elderly human donors indicates limited influence of microdamage burden or collagen cross-link concentration on trabecular bone mechanical properties. These data suggest that bone volume fraction is the predominant determinant of trabecular bone mechanical properties. doi:10.1016/j.bone.2009.01.312
406 Which subchondral bone measure is the best predictor of cartilage damage? D. Dore, C. Ding, G. Jones Menzies Research Institute, Hobart, TAS, Australia Background: It is widely accepted that subchondral bone plays a central role in the pathogenesis of osteoarthritis (OA). Evidence suggests that subchondral bone changes precede cartilage damage, indicating bone changes may be an early stage of OA. The objective of this study was to describe the association of baseline areal and volumetric knee subchondral bone mineral density (sBMD), tibial bone size, and bone marrow lesions with knee cartilage defect progression and cartilage volume loss in adult males and females. Methods: A total of 390 subjects (mean age 63 years, range 51– 79) were measured at baseline and approximately 2.5 years later. Knee cartilage volume, cartilage defects (range, 0–4), and bone size were determined using T1-weighted fat saturation MRI. Bone marrow lesions (range, 0–3) were determined using T2-weighted MRI images. Areal sBMD was assessed by DXA. Volumetric sBMD was calculated as: bone mineral content / (bone area × region of interest). Results: For the medial compartment, baseline bone size was positively associated with increases in tibiofemoral cartilage defects (odds ratio [OR] 2.6 per change in SD, P < 0.01) and negatively associated with annual cartilage volume change (β = − 0.01, P < 0.01). Baseline tibial and femoral bone marrow lesions were positively associated with tibial and femoral cartilage defect increases (OR 1.7 per grade, P = 0.01; OR 2.3 per grade, P < 0.01, respectively) and negatively associated with compartment specific cartilage volume change (β = − 1.0, P = 0.024; β = − 2.5, P < 0.01, respectively). Similar results were observed for the lateral compartment. Neither, areal or volumetric sBMD at baseline were associated with increases in cartilage defects or cartilage volume loss. Conclusions: Both tibial bone area and bone marrow lesions at baseline predict compartment specific cartilage defect progression and cartilage volume loss. The lack of association between sBMD and
cartilage damage suggests that tibial bone size and bone marrow lesions may be the preferred subchondral bone targets for intervention. doi:10.1016/j.bone.2009.01.313
407 Anti tumor necrotic factor agents promote the ability of the BMP-2 induced ectopic bone formation Y. Eguchi, S. Wakitani, Y. Imai, Y. Naka, Y. Hashimoto, K. Takaoka Department of Orthopaedics, Osaka City University Graduate School of Medicine, Osaka, Japan Tumor necrosis factor-α (TNF-α) plays key role in the regulation of inflammatory synovitis and the subsequent destruction of cartilage and bone in rheumatoid arthritis (RA). Etanercept (ETN), which is a recombinant human soluble TNF receptor and inhibits TNF action, is effective in the treatment of RA. We investigated the effect ETN on rhBMP2 induced ectopic bone formation in vivo. A block copolymer composed of poly-d, l-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG polymer) was used as the delivery system. Each polymer disc (6 mm, 30 mg) containing 5 μg rhBMP-2 were implanted into the left dorsal muscle pouch of mice (n=5). ETN were subcutaneously injected (25 mg/human=12.5 μg/mouse) twice per week in a dose-dependent manner (group1; placebo, group2; 12.5×1/ 1000, group3; 12.5×1/10, group4; 12.5, and group5; 12.5 ×10) as systemic administration groups, whereas the single dose of ETN were also embedded in each polymer with rhBMP-2 in the same manner as a local administration groups. All implants were increased radiodensity at 3 weeks posttransplantation, consistent with a significant increase of bone mineral contents (BMC) of ossicles. Bone histomorphology exhibited a significant increase in both trabecular BV/TV and osteoblast number and a significant decrease in osteoclast number dose-dependently both systemic and local administration of ETN. No significant difference in body weight and serum data (AlP, Ca, P) among groups was observed during the experimental period. These data suggested that the optimal dose of ETN systemically or locally enhanced the bone inducing capacity of rhBMP-2 with no apparent systemic adverse effect. doi:10.1016/j.bone.2009.01.314
408 Human versus sheep vertebral cortical bone strain and intervertebral disc mechanical properties J.J. Costia, R.M. Stanleya, H.J. Tettisa, N.L. Fazzalarib a Orthopaedics, Repatriation General Hospital and Flinders University, Daw Park, SA, Australia b Bone and Joint Research Laboratory, Institute of Medical and Veterinary Science and Hanson Institute, Adelaide, SA, Australia Introduction: Animal models are increasingly being used for research studies of the spine, and the sheep lumbar motion segment has been shown to have morphological and biochemical similarities to human segments. However, the differences in vertebral cortical bone principal strains and disc mechanical (stiffness and phase angle) properties have not been quantified. Methods: Twenty, lumbar disc segments from 14 human spines and six Merino wethers were obtained. Strain gauge rosettes were bonded to the vertebral cortical bone surface of the inferior, disc-endplate boundary at three locations: right/left lateral and anterior. Each disc was equilibrated under an 0.2 MPa compressive preload in a 0.15 M PBS bath and subjected to 10 sinusoidal cycles in compression (1 MPa) at 0.5 Hz. Principal
Abstracts / Bone 44 (2009) S142–S161
performance liquid chromatography. Non-parametric tests were used (Spearman coefficient correlation r′). Linear crack density (#/mm2) and diffuse damage area density (%) increased with age (r′ = 0.36, p = 0.01, r′ = 0.32, p = 0.022, respectively), as did the PYD/DPD ratio (r′ = 0.31, p = 0.028). Elastic modulus and ultimate strength decreased with age (r′ = − 0.36, p = 0.01, r′ = − 0.39, p = 0.01, respectively), whereas post-yield strain was unchanged. BV/TV was strongly correlated with elastic modulus (r′ = 0.66, p < 0.001) and ultimate strength (r′ = 0.74, p < 0.001). The elastic modulus was weakly correlated to mean crack length (r′ = 0.30, p = 0.036), but otherwise not associated with pre-existing microdamage. Collagen cross-link concentrations were not associated with mechanical properties. PYD concentration was positively correlated to linear microcrack density (r′ = 0.33, p = 0.017) and to total microcrack density (r′ = 0.36, p = 0.008), whereas PYD and DPD were negatively correlated to mean microcrack length (r′ = − 0.30, p = 0.029 and r′ = − 0.28, p = 0.046, respectively). PEN concentration was not associated with microdamage. In summary, this study of trabecular bone from elderly human donors indicates limited influence of microdamage burden or collagen cross-link concentration on trabecular bone mechanical properties. These data suggest that bone volume fraction is the predominant determinant of trabecular bone mechanical properties. doi:10.1016/j.bone.2009.01.312
406 Which subchondral bone measure is the best predictor of cartilage damage? D. Dore, C. Ding, G. Jones Menzies Research Institute, Hobart, TAS, Australia Background: It is widely accepted that subchondral bone plays a central role in the pathogenesis of osteoarthritis (OA). Evidence suggests that subchondral bone changes precede cartilage damage, indicating bone changes may be an early stage of OA. The objective of this study was to describe the association of baseline areal and volumetric knee subchondral bone mineral density (sBMD), tibial bone size, and bone marrow lesions with knee cartilage defect progression and cartilage volume loss in adult males and females. Methods: A total of 390 subjects (mean age 63 years, range 51– 79) were measured at baseline and approximately 2.5 years later. Knee cartilage volume, cartilage defects (range, 0–4), and bone size were determined using T1-weighted fat saturation MRI. Bone marrow lesions (range, 0–3) were determined using T2-weighted MRI images. Areal sBMD was assessed by DXA. Volumetric sBMD was calculated as: bone mineral content / (bone area × region of interest). Results: For the medial compartment, baseline bone size was positively associated with increases in tibiofemoral cartilage defects (odds ratio [OR] 2.6 per change in SD, P < 0.01) and negatively associated with annual cartilage volume change (β = − 0.01, P < 0.01). Baseline tibial and femoral bone marrow lesions were positively associated with tibial and femoral cartilage defect increases (OR 1.7 per grade, P = 0.01; OR 2.3 per grade, P < 0.01, respectively) and negatively associated with compartment specific cartilage volume change (β = − 1.0, P = 0.024; β = − 2.5, P < 0.01, respectively). Similar results were observed for the lateral compartment. Neither, areal or volumetric sBMD at baseline were associated with increases in cartilage defects or cartilage volume loss. Conclusions: Both tibial bone area and bone marrow lesions at baseline predict compartment specific cartilage defect progression and cartilage volume loss. The lack of association between sBMD and
cartilage damage suggests that tibial bone size and bone marrow lesions may be the preferred subchondral bone targets for intervention. doi:10.1016/j.bone.2009.01.313
407 Anti tumor necrotic factor agents promote the ability of the BMP-2 induced ectopic bone formation Y. Eguchi, S. Wakitani, Y. Imai, Y. Naka, Y. Hashimoto, K. Takaoka Department of Orthopaedics, Osaka City University Graduate School of Medicine, Osaka, Japan Tumor necrosis factor-α (TNF-α) plays key role in the regulation of inflammatory synovitis and the subsequent destruction of cartilage and bone in rheumatoid arthritis (RA). Etanercept (ETN), which is a recombinant human soluble TNF receptor and inhibits TNF action, is effective in the treatment of RA. We investigated the effect ETN on rhBMP2 induced ectopic bone formation in vivo. A block copolymer composed of poly-d, l-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG polymer) was used as the delivery system. Each polymer disc (6 mm, 30 mg) containing 5 μg rhBMP-2 were implanted into the left dorsal muscle pouch of mice (n=5). ETN were subcutaneously injected (25 mg/human=12.5 μg/mouse) twice per week in a dose-dependent manner (group1; placebo, group2; 12.5×1/ 1000, group3; 12.5×1/10, group4; 12.5, and group5; 12.5 ×10) as systemic administration groups, whereas the single dose of ETN were also embedded in each polymer with rhBMP-2 in the same manner as a local administration groups. All implants were increased radiodensity at 3 weeks posttransplantation, consistent with a significant increase of bone mineral contents (BMC) of ossicles. Bone histomorphology exhibited a significant increase in both trabecular BV/TV and osteoblast number and a significant decrease in osteoclast number dose-dependently both systemic and local administration of ETN. No significant difference in body weight and serum data (AlP, Ca, P) among groups was observed during the experimental period. These data suggested that the optimal dose of ETN systemically or locally enhanced the bone inducing capacity of rhBMP-2 with no apparent systemic adverse effect. doi:10.1016/j.bone.2009.01.314
408 Human versus sheep vertebral cortical bone strain and intervertebral disc mechanical properties J.J. Costia, R.M. Stanleya, H.J. Tettisa, N.L. Fazzalarib a Orthopaedics, Repatriation General Hospital and Flinders University, Daw Park, SA, Australia b Bone and Joint Research Laboratory, Institute of Medical and Veterinary Science and Hanson Institute, Adelaide, SA, Australia Introduction: Animal models are increasingly being used for research studies of the spine, and the sheep lumbar motion segment has been shown to have morphological and biochemical similarities to human segments. However, the differences in vertebral cortical bone principal strains and disc mechanical (stiffness and phase angle) properties have not been quantified. Methods: Twenty, lumbar disc segments from 14 human spines and six Merino wethers were obtained. Strain gauge rosettes were bonded to the vertebral cortical bone surface of the inferior, disc-endplate boundary at three locations: right/left lateral and anterior. Each disc was equilibrated under an 0.2 MPa compressive preload in a 0.15 M PBS bath and subjected to 10 sinusoidal cycles in compression (1 MPa) at 0.5 Hz. Principal